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Hpsc-derived Tissue-resident Macrophage Model Reveals Differential Responses Of Macrophages To Zikv And Deny Infection

Title: An Hpsc-derived Tissue-resident Macrophage Model Reveals Differential Responses Of Macrophages To Zikv And Deny Infection.
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Name(s): Lang, Jianshe, author
Cheng, Yichen, author
Rolfe, Alyssa, author
Hammack, Christy, author
Vera, Daniel, author
Kyle, Kathleen, author
Wang, Jingying, author
Meissner, Torsten B., author
Ren, Yi, author
Cowan, Chad, author
Tang, Hengli, author
Type of Resource: text
Genre: Journal Article
Text
Journal Article
Date Issued: 2018-08-14
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Zika virus (ZIKV) and dengue virus (DENV) are two closely related flaviviruses that lead to different clinical outcomes. The mechanism for the distinct pathogenesis of ZIKV and DENV is poorly understood. Here, we investigate ZIKV and DENV infection of macrophages using a human pluripotent stem cell (hPSC)-derived macrophage model and discover key virus-specific responses. ZIKV and DENV productively infect hPSC-derived macrophages. DENV, but not ZIKV, infection of macrophages strongly activates macrophage migration inhibitory factor (MIF) secretion and decreases macrophage migration. Neutralization of MIF leads to improved migratory ability of DENV-infected macrophages. In contrast, ZIKV-infected macrophages exhibit prolonged migration and express low levels of pro-inflammatory cytokines and chemokines. Mechanistically, ZIKV disrupts the nuclear factor kappa B (NF-kappa B)-MIF positive feedback loop by inhibiting the NF-kappa B signaling pathway. Our results demonstrate the utility of hPSC-derived macrophages in infectious disease modeling and suggest that the distinct impact of ZIKV and DENV on macrophage immune response may underlie different pathogenesis of Zika and dengue diseases.
Identifier: FSU_libsubv1_wos_000441583100006 (IID), 10.1016/j.stemcr.2018.06.006 (DOI)
Keywords: activation, cells, disease, expression, mice, blood, nf-kappa-b, virus, dengue, migration inhibitory factor
Publication Note: The publisher’s version of record is available at https://doi.org/10.1016/j.stemcr.2018.06.006
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_libsubv1_wos_000441583100006
Owner Institution: FSU
Is Part Of: Stem Cell Reports.
2213-6711
Issue: iss. 2, vol. 11

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Lang, J., Cheng, Y., Rolfe, A., Hammack, C., Vera, D., Kyle, K., … Tang, H. (2018). An Hpsc-derived Tissue-resident Macrophage Model Reveals Differential Responses Of Macrophages To Zikv And Deny Infection. Stem Cell Reports. Retrieved from http://purl.flvc.org/fsu/fd/FSU_libsubv1_wos_000441583100006